A tooth is an organ having enamel in the outermost layer and dentin in the inner layer, both of which are hard tissues, odontoblasts inner side of the dentin, which produces dentin, and dental pulp in the central portion, and may be lost by dental caries, periodontal diseases or the like.
Teeth are functional units that are formed by induction during the developmental process of the fetal stage and constructed with plural cell types, and they are thought to be the same as organs or internal organs. Therefore, teeth could not be generated by stem cell system in which various cells are generated from a single stem cell such as a hematopoietic stem cell or a mesenchymal stem cell in the adult body. At results, teeth cannot be regenerated solely by stem cell transplantation (stem cell transplantation therapy) which is currently under development by regenerative medicine.
Therefore, studies have been conducted recently with a central focus on tooth regeneration by transplanting a reconstituted tooth germ obtained by reconstituting a tooth germ using isolated tooth germ cells.
For example, in J. Dent. Res., 2002, Vol. 81(10), pp. 695-700, it is disclosed that a tooth-like tissue is regenerated by transplanting cells, such as epithelial cells isolated from a tooth germ and mesenchymal dental follicle cells, with a biodegradative carrier into an abdominal cavity of a rat.
As a method of regenerating a tooth germ, it is described, for example, in Japanese Patent Application Laid-open (JP-A) No. 2004-331557, that tooth germ cells isolated from a living body are cultured in the presence of biologically active substances such as fibroblast growth factors and the like. In JP-A No. 2004-357567, it is proposed that at least one type of cells selected from tooth germ cells and cells which can be differentiated into these tooth germ cells, both of them are isolated from a living body, are cultured along with a fibrin-containing carrier, and it is described that a “tooth” having a specific shape is formed by using a fibrin-containing carrier having the desired shape for the tooth germ.
In US Patent Application Publication No. 2002/0119180 and US Patent Application Publication No. 2004/0219489, a method of forming teeth is disclosed that includes seeding a cell mixture of a tooth germ containing dentin forming mesenchymal cells derived from dental pulp and epithelial cells which contribute to enamel formation, from the mandible of a 6 month-old pig, into a scaffold which is a solidified biodegradable polymer containing a polyglycolic acid/polyacetic acid copolymer; and transplanting it into an animal body. Here, it is described that a “tooth” having a specific shape is formed by using a scaffold having the desired shape for the tooth germ.
Further, in International Publication (WO) No. 2005/014070, a method of tooth regeneration for treating a patient with bone loss or damage is disclosed. According to this method, a bone is formed by seeding mesenchymal cells in a polyglycolic acid mesh carrier and then laminating the carrier with epithelial cells and collagen or wrapping it with an epithelial cell sheet. Further, in WO 2005/014070, a carrier is used to construct the shape of a bone.
In WO 2006/129672, a tooth producing method is described, the method including obtaining cell masses which are made of epithelial cells and mesenchymal cells from a dental germ, respectively; contacting these cell masses with each other in a collagen gel; culturing these cell masses under contacting conditions so as to obtain a tooth having a specific cell arrangement for a tooth.
However, in the above techniques, in order to regenerate a tooth or a tooth germ, tooth germ cells or cells capable of differentiating thereinto are obtained from a living body. In such a technique in which cells collected from a living body are used, the number of cells which can be obtained is sometimes insufficient. Further, the source of supply of the cells is sometimes limited.
To exert a function as a tissue, it is indispensable that multiple types of cells constituting the tissue be arranged (cell arrangement) at appropriate relative positions and have directionality as the tissue.